title: Image-based noninvasive evaluation of colorectal mucosal injury in sheep after topical application of microbicides.
abstract: BACKGROUND
  Successful development of topical rectal microbicides requires preclinical evaluation in suitable large animal models. Our previous studies have demonstrated the benefits of high-resolution optical coherence tomography (OCT) to visualize subclinical microbicide toxicity in the sheep vagina. In the current study, we evaluated the potential application of colonoscopy and OCT to visualize and quantify the effects of topical products on sheep colorectal tissue, as assessed by advanced imaging techniques.
  
  
  METHODS
  Yearling virginal female sheep were treated rectally with a single 8-mL dose of 0.2% benzalkonium chloride (BZK) solution or phosphate-buffered saline control. Imaging was performed before and 30 minutes after treatment. Colonoscopy findings were evaluated based on mucosal disruption. Optical coherence tomography images were graded based on the integrity of the mucosal layer. Biopsies collected after treatment were evaluated by histology for validation of OCT scoring.
  
  
  RESULTS
  Mucosal disruption was observed by colonoscopy in BZK-treated animals, whereas none was present in controls. In contrast to colonoscopy, high-resolution in-depth OCT imaging provided visualization of the morphology of the mucosal layer and underlying muscularis, thus enabling detection of microscopic abnormalities. Noninvasive quantification of drug-induced injury after validation of the scoring system (categories 1, 2, 3) showed increased scores after treatment with BZK (P < 0.001), indicating mucosal injury.
  
  
  CONCLUSIONS
  High-resolution OCT can be used as highly sensitive tool to evaluate rectal microbicide effects. Because the sheep rectum has both gross and microscopic similarities to the human, this model is a useful addition to current methods of rectal product toxicity.
authors.affiliation: From the *Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX; †Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX; ‡Department of Neuroscience & Cell Biology, University of Texas Medical Branch, Galveston, TX; §Department of Pediatrics, University of Texas Medical Branch, Galveston, TX; ¶Sealy Center for Vaccine, University of Texas Medical Branch, Galveston, TX; ∥Internal Medicine, Division of Gastroenterology, University of Texas Medical Branch, Galveston, TX; **Department of Pathology, University of Texas Medical Branch, Galveston, TX; and ††Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX.
authors.forename: Kathleen Listiak
authors.initials: KL
authors.lastname: Vincent
authors.forename: Gracie
authors.initials: G
authors.lastname: Vargas
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
authors.forename: Valerie
authors.initials: V
authors.lastname: Galvan-Turner
authors.forename: Jamal I
authors.initials: JI
authors.lastname: Saada
authors.forename: Gabriel H
authors.initials: GH
authors.lastname: Lee
authors.forename: Elena
authors.initials: E
authors.lastname: Sbrana
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
mesh_terms: D001003:Anal Canal / Q000473:pathology*; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D003113:Colonoscopy; D004195:Disease Models, Animal; D005260:Female; D007413:Intestinal Mucosa / Q000473:pathology*; D012756:Sheep; D041623:Tomography, Optical Coherence; D014621:Vagina / Q000473:pathology
chemical_list: D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds